Pillararene incorporated metal–organic frameworks for supramolecular recognition and selective separation

Crystalline frameworks containing incorporated flexible macrocycle units can afford new opportunities in molecular recognition and selective separation. However, such functionalized frameworks are difficult to prepare and challenging to characterize due to the flexible nature of macrocycles, which limits the development of macrocycle-based crystalline frameworks. Herein, we report the design and synthesis of a set of metal–organic frameworks (MOFs) containing pillar[5]arene units. The pillar[5]arene units were uniformly embedded in the periodic frameworks. Single crystal X-ray diffraction analysis revealed an interpenetrated network that appears to hinder the rotation of the pillar[5]arene repeating units in the frameworks, and it therefore resulted in the successful determination of the precise pillar[5]arene host structure in a MOF crystal. These MOFs can recognize paraquat and 1,2,4,5-tetracyanobenzene in solution and selectively remove trace pyridine from toluene with relative ease. The work presented here represents a critical step towards the synthesis of macrocycle-incorporated crystalline frameworks with well-defined structures and functional utility.

1. Sentences in lines 50-54 may be potentially misleading to the reader. It is difficult for me to agree with the assertion that all frameworks containing macrocyclic subunits are challenging to characterize. It is necessary to clarify that this statement pertains only to flexible macrocycles. 2. The authors need to provide further clarification on why the rotation of the PA subunit hinders the determination of a single crystal structure. The references cited by the authors (Ref. 27,31,32,39,and 40) do not provide clear evidence to support this claim. For instance, it would be helpful to know if it is also challenging to identify the SC-XRD of a crystal packed solely with pure PA. (S24-25) 3. In the flexible CE-based MOF, macrocycle dynamics were previously studied through 2H SSNMR (as reported in J. Am. Chem. Soc. 2014, 136, 20, 7403-7409). Is there any data available that can directly demonstrate the rotation of the PA ring in MeP5-MOFs, as presented in the aforementioned study? 4. It is widely recognized that SCXRD at low temperatures can limit the mobility of subunits within crystals and provide more precise structural information (Chem. Soc. Rev., 2004, 33, 490-500). Therefore, the authors must supply SCXRD data collected below 193 K for each framework. 5. The cartoon presented in Fig 1a might impede an intuitive comprehension of these MOF structures and introduce ambiguity to the nomenclature. It is crucial to explicitly specify which moiety each MOF contains and the corresponding structural characteristics. 6. For "After numerous attempts" on line 145, this is an unnecessary sentence. 7. For "The ability … limits their motion" on lines 152-154, this is a reasonable claim, but authors also need direct experimental data to prove it. 8. The authors need to offer further background information on why the crystal's absolute structure can be justified if the crystal's SCXRD has a Flack constant below 0.3. 9. Regarding the statement "Take in concert, ... effectively by SCXRD" in lines 176-180, the authors require concrete evidence to support their assertions. For instance, would a deinterpenetrated MeP5-MOF-2 yield the same outcome as 1, 3, and 4? Additionally, if an extra moiety capable of restricting the pore space in MeP5-MOF-1, 3, and 4 is integrated into the linker, would it enable the identification of the PA ring of the pillar? 10. The photographs in Figures 4a and b are not distinctly displaying the color differences among the crystals because of the varying background brightness levels in the two images. 11. In addition to the fluorescence spectra of the PA unit, the authors should also demonstrate whether guest adsorption alters the fluorescence spectra of each MOF. 12. The author needs to clarify the toluene/pyridine separation condition of other studies to be compared. For example, in Ref. S14, 5.00 mg of adsorbent was added to 10 mL of 100:1 v/v Tol/Py mixture. 13. Regarding the statement "We thus conclude … Py/Tol mixture separation capability" on lines 299-301, the author needs to be cautious about this claim. The experimental conditions for the Tol/Py separation performance experiment in this work differ from those of the studies used for comparison by the authors. 14. The author should provide data comparing the performance of their MOF with currently available commercial Tol/Py separation processes. 15. The authors should provide additional data on the Tol/Py separation experiments, including information on the efficiency of the MOF adsorbents in bulk conditions, as well as their recyclability and stability in the Tol/Py separation process. 16. The authors should provide experimental data on the porosity of MeP5-MOFs, ideally through gas adsorption/desorption isotherm measurements.
Reviewer #2 (Remarks to the Author): In this work, the authors present the synthesis of a series of MeP5-MOF-n single crystals based on pillar [5]arene-based ligands through a "pillar-layer" strategy. The introduction of macrocycle units into MOF frameworks exhibited intriguing guest recognition and separation properties. The efforts are impressive to grow and pick the single cyrstals and refine the SCXRD structure of complicated macrocycle-based MOFs with soft and disordered pillar[5]arene units. The current work is suitable for publication in Nature Communication after following minor revisions: 1. It is recommended that the authors revies the illustration figures for better clarity. In the current state, it is hard to distinguish different linkers of the same series (like MeP5BPY/MeP5BPPY and H4TPE/H4TPPE). I recommend using different colors for the same series of linkers (for example red for MeP5BPy and orange for MeP5BPPY, blue for H4TPE and purple for H4TPPE). 2. In Figure S27, some C-C bonds on the benzene rings of ligands seems strange, showing squareshaped bonding. This Figure should be revised. 3. SXRD indicated rigid framework backbone structures of the MeP5-MOF-n series. Is there any information about the permanent porosity of these MOFs from gas sorption analysis? How is the stability of these MOFs towards thermal treatment and ambient moisture? 4. MeP5-MOF-1 showed higher guest uptake than MeP5-MOF-2, what's the possible reason? 5. For Py and Tol separation, simulation and SCXRD refinement indicated that Py was most likely captured by the cavities of pillar[5]arene rings, while Tol was instead adsorbed between TPPE layers. Such distinct adsorption behaviors should be discussed in more detail from a chemical perspective to better understand the underlying guest separation mechanism. 6. What's the guest sorption and separation properties of MeP5-MOF-3 and MeP5-MOF-4? No related properties were examined in the current manuscript. 7. The determination of flexible groups in the structure through SCXRD may be more accurate at lower temperatures. Can SCXRD at lower temperatures (e.g., 80 K) be tested? 8. The "Mole Ratio" in Fig. 4 should be added with error bar. 9. The format of references should be noted, such as "macrocycle-based" in reference [16] and "clathrochelate-based" in reference [46].

Reviewer #3 (Remarks to the Author):
The authors reported the synthesis of pillarene-based MOFs and their use in host-guest recognition and separation of small molecules. Steric effect has been effective in hindering the rotation of linker pillars that resulted in the successful resolution of macrocyclic pillarenes within the MOF structure, which has been a challenge in previous related studies. The structural advance provides unequivocal evidence about the presence and location of macrocycles within the framework. The pillarene-MOFs have shown improved and selective adsorption towards guests, and in one case being applied towards the separation of pyridine/toluene. Structural characterization was done thoroughly and thoughtfully. The authors however didn't address the stability of the resulting MOFs, which raises substantial questions about their value towards host-guest binding and separation. The manuscript is very well written overall, though I recommend the authors to address the following comments before its acceptance: 1. Porosity. For the interpenetrated MOF vs. the non-interpenetrated ones, are there significant differences in terms of surface area and pore size? Have the authors run BET studies of those MOFs? 2. The PXRD pattern of MOFs changed significantly before and after exposure to different guests. The authors attributed the changes to the dynamics within the MOF. This is quite handwaving. Can authors give more insight into such changes? This raises the question about the stability of the MOF towards solvents, vacuum, temperature etc. Are the host-guest responses reversible, i.e., can the PXRD be reverted after removal of guests? If not, what is the nature of the solid-state changes? It is reasonably to believe that the MOFs are assembled through the coordination between pyridyl groups of the pillars and the Zn metal centers, which is weak and may relate to the intrinsic instability of such MOFs. The authors are also suggested to run DSC to probe the thermal stability of the crystalline phases. 3. On a related note, as stated, better separation was achieved by repeated treatment of the Py/Tol mixture with fresh batches of MOF. Does the need of using fresh MOF also relate to the instability of the MOFs? The significance of their utility for separation will be greatly limited since it is of no practicality if the adsorbent can't be recycled.
Reviewer #4 (Remarks to the Author): In this manuscript, the authors reported a set of metal-organic frameworks (MOFs) containing incorporated pillar[5]arene units and used them in molecular recognition and selective separation. Since numerous macrocycle-incorporated MOFs cannot precisely locate the macrocycle moieties in the frameworks due to the rotation of macrocycles' repeat units, the structure resolution of such MOFs is always a challenge. In this work, the authors altered the sizes of pillar[5]arene struts and obtained the atomically precise structures of pillar[5]arene-based MOFs characterized by single crystal X-ray diffraction. They found that the interpenetrated network limited the rotation of the pillar[5]arene repeat units in the frameworks. It is an interesting phenomenon, which is helpful for constructing macrocycle-incorporated crystalline frameworks in other cases. Their MOFs can recognize paraquat and 1,2,4,5-tetracyanobenzene in solution and selectively remove trace pyridine from toluene. This manuscript is well written, and clearly illustrates the structure-property relationships with solid evidence. Therefore, I recommend this work to be accepted for publication after considering the following minor comments.
1. Page 6, "After numerous attempts, single crystals of MeP5-MOF-2 were obtained utilizing a solvo-thermal procedure, strut MeP5BPPy was combined with H4TPPE and Zn(NO3)2.6H2O." Here, the authors should describe the conditions of single crystal growth with more details. 2. Page 7, "Single crystals of both species were obtained. The Flack parameters for pS-MeP5-MOF-2 and pR-MeP5-MOF-2 were found to be 0.28(2) and 0.26(3). These values are less than 0.30, allowing their absolute structures to be determined with confidence." Here, the authors should cite the corresponding references about Flack parameters. 3. In this manuscript, the authors used TPE ligands as the layers to construct their pillar [5]